A cell-permeable indolyl-hydantoin compound that simultaneously inhibits the interaction of both, MDM2 and MDMX with p53 (IC50 = 17.3 and 24.7nM, respectively, in vitro). Releases p53 from MDMX inhibition, stabilizes it, and fully restores its function. Shown to be far more superior to Nutlin-3a in blocking p53 interaction with MDMX. Binds to Phe, Trp, and Leu sub-pockets on the surface of MDMX and MDM2, and promotes MDMX and MDM2 dimer formation. Shown to induce cell cycle arrest in G1 and G2 phases. Also reported to induce apoptosis in several tumor cell lines expressing wild-type p53/MDMX (~10-20uM). Its actions are not believed to be due to any genotoxic stress.
Primary Target:MDMX
Secondary Target:MDM2
Solubility:DMSO
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months after receipt at -20°C. Reconstitute with sterile buffer or ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
